![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
AA Reszka, JC Bulinski, EG Krebs and EH Fischer
Department of Biochemistry, University of Washington, Seattle 98195, USA.
The extracellular signal-regulated kinases (ERKs) 1 and 2 are mitogen- activated protein kinases that act as key components in a signaling cascade linking growth factor receptors to the cytoskeleton and the nucleus. ERK2 mutants have been used to alter cytoskeletal regulation in Chinese hamster ovary cells without affecting cell growth or feedback signaling. Mutation of the unique loop L6 (residues 91-95), which is in a portion of the molecule that is cryptic upon the binding of ERK2 to the microtubules (MTs), generated significant morphological alterations. Most notable phenotypes were observed after expression of a combined mutant incorporating changes to both L6 and the TEY phosphorylation lip, including a 70% increase in cell spreading. Actin stress fibers in these cells, which normally formed a single broad parallel array, were arranged in three or more orientations or in fan- like arrays. MTs, which ordinarily extend longitudinally from the centrosome, spread radially, covering a larger surface area. Single, but not the double, mutations of the Thr and Tyr residues of the TEY phosphorylation lip caused a ca. 25% increase in cell spreading, accompanied by a threefold increase in chemotactic cell migration. Mutation of Lys-52 triggered a 48% increase in cell spreading but no alteration to chemotaxis. These findings suggest that wild-type ERK2 inhibits the organization of the cytoskeleton, the spreading of the cell, and chemotactic migration. This involves control of the orientation of actin and MTs and the positioning of focal adhesions via regulatory interactions that may occur on the MTs.
This article has been cited by other articles:
|
|
 |
|
  Y. Zhang, X.-T. Bai, K.-Y. Zhu, Y. Jin, M. Deng, H.-Y. Le, Y.-F. Fu, Y. Chen, J. Zhu, A. T. Look, et al. In Vivo Interstitial Migration of Primitive Macrophages Mediated by JNK-Matrix Metalloproteinase 13 Signaling in Response to Acute Injury J. Immunol., August 1, 2008; 181(3): 2155 - 2164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Agasse, L. Bernardino, H. Kristiansen, S. H. Christiansen, R. Ferreira, B. Silva, S. Grade, D. P.D. Woldbye, and J. O. Malva Neuropeptide Y Promotes Neurogenesis in Murine Subventricular Zone Stem Cells, June 1, 2008; 26(6): 1636 - 1645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bendetz-Nezer and R. Seger Role of Non-phosphorylated Activation Loop Residues in Determining ERK2 Dephosphorylation, Activity, and Subcellular Localization J. Biol. Chem., August 24, 2007; 282(34): 25114 - 25122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Aoukaty and R. Tan Role for Glycogen Synthase Kinase-3 in NK Cell Cytotoxicity and X-Linked Lymphoproliferative Disease J. Immunol., April 15, 2005; 174(8): 4551 - 4558. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. McDaid, L. Lopez-Barcons, A. Grossman, M. Lia, S. Keller, R. Perez-Soler, and S. Band Horwitz Enhancement of the Therapeutic Efficacy of Taxol by the Mitogen-Activated Protein Kinase Kinase Inhibitor CI-1040 in Nude Mice Bearing Human Heterotransplants Cancer Res., April 1, 2005; 65(7): 2854 - 2860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Nilsen and R. D. Brinton Divergent impact of progesterone and medroxyprogesterone acetate (Provera) on nuclear mitogen-activated protein kinase signaling PNAS, September 2, 2003; 100(18): 10506 - 10511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Stockton and B. S. Jacobson Modulation of Cell-Substrate Adhesion by Arachidonic Acid: Lipoxygenase Regulates Cell Spreading and ERK1/2-inducible Cyclooxygenase Regulates Cell Migration in NIH-3T3 Fibroblasts Mol. Biol. Cell, July 1, 2001; 12(7): 1937 - 1956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Pearson, F. Robinson, T. Beers Gibson, B.-e Xu, M. Karandikar, K. Berman, and M. H. Cobb Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions Endocr. Rev., April 1, 2001; 22(2): 153 - 183. [Abstract] [Full Text]
|
|
|
|
 |
|
 H. Reuveni, T. Geiger, B. Geiger, and A. Levitzki Reversal of the Ras-induced Transformed Phenotype by HR12, a Novel Ras Farnesylation Inhibitor, Is Mediated by the Mek/Erk Pathway J. Cell Biol., December 11, 2000; 151(6): 1179 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Jin, S. He, V. Wörpel, S. J. Ryan, and D. R. Hinton Promotion of Adhesion and Migration of RPE Cells to Provisional Extracellular Matrices by TNF-{alpha} Invest. Ophthalmol. Vis. Sci., December 1, 2000; 41(13): 4324 - 4332. [Abstract] [Full Text]
|
|
|
|
 |
|
 I. A. Yamboliev, K. M. Wiesmann, C. A. Singer, J. C. Hedges, and W. T. Gerthoffer Phosphatidylinositol 3-kinases regulate ERK and p38 MAP kinases in canine colonic smooth muscle Am J Physiol Cell Physiol, August 1, 2000; 279(2): C352 - C360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ku and K. E. Meier Phosphorylation of Paxillin via the ERK Mitogen-activated Protein Kinase Cascade in EL4 Thymoma Cells J. Biol. Chem., April 6, 2000; 275(15): 11333 - 11340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. T. Kampen, S. Stafford, T. Adachi, T. Jinquan, S. Quan, J. A. Grant, P. S. Skov, L. K. Poulsen, and R. Alam Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases Blood, March 15, 2000; 95(6): 1911 - 1917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. CAMPS, A. NICHOLS, and S. ARKINSTALL Dual specificity phosphatases: a gene family for control of MAP kinase function FASEB J, January 1, 2000; 14(1): 6 - 16. [Abstract] [Full Text]
|
|
|
|
|
|
D. B. Polk and W. Tong Epidermal and hepatocyte growth factors stimulate chemotaxis in an intestinal epithelial cell line Am J Physiol Cell Physiol, December 1, 1999; 277(6): C1149 - C1159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, G. Dobrowolska, L. D. Aicher, M. Chen, J. H. Wright, P. Drueckes, E. L. Dunphy, E. S. Munar, and E. G. Krebs Expression of the Casein Kinase 2 Subunits in Chinese Hamster Ovary and 3T3 L1 Cells Provides Information on the Role of the Enzyme in Cell Proliferation and the Cell Cycle J. Biol. Chem., November 12, 1999; 274(46): 32988 - 32996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Wright, E. Munar, D. R. Jameson, P. R. Andreassen, R. L. Margolis, R. Seger, and E. G. Krebs Mitogen-activated protein kinase kinase activity is required for the G2/M transition of the cell cycle in mammalian fibroblasts PNAS, September 28, 1999; 96(20): 11335 - 11340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Mills, N. L. Stone, and R. N. Pittman Extranuclear Apoptosis: The Role of the Cytoplasm in the Execution Phase J. Cell Biol., August 23, 1999; 146(4): 703 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Montesano, J. V. Soriano, G. Hosseini, M. S. Pepper, and H. Schramek Constitutively Active Mitogen-activated Protein Kinase Kinase MEK1 Disrupts Morphogenesis and Induces an Invasive Phenotype in Madin-Darby Canine Kidney Epithelial Cells Cell Growth Differ., May 1, 1999; 10(5): 317 - 332. [Abstract] [Full Text]
|
|
|
|
|
|
N. Suzuki, K. Del Villar, and F. Tamanoi Farnesyltransferase inhibitors induce dramatic morphological changes of KNRK cells that are blocked by microtubule interfering agents PNAS, September 1, 1998; 95(18): 10499 - 10504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Aplin, A. Howe, S. K. Alahari, and R. L. Juliano Signal Transduction and Signal Modulation by Cell Adhesion Receptors: The Role of Integrins, Cadherins, Immunoglobulin-Cell Adhesion Molecules, and Selectins Pharmacol. Rev., June 1, 1998; 50(2): 197 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Camps, A. Nichols, C. Gillieron, B. Antonsson, M. Muda, C. Chabert, U. Boschert, and S. Arkinstall Catalytic Activation of the Phosphatase MKP-3 by ERK2 Mitogen-Activated Protein Kinase Science, May 22, 1998; 280(5367): 1262 - 1265. [Abstract] [Full Text]
|
|
|
|
|
|
S. Zhang, M. C. Y. Chang, D. Zylka, S. Turley, R. Harrison, and E. A. Turley The Hyaluronan Receptor RHAMM Regulates Extracellular-regulated Kinase J. Biol. Chem., May 1, 1998; 273(18): 11342 - 11348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O Calderini, L Bogre, O Vicente, P Binarova, E Heberle-Bors, and C Wilson A cell cycle regulated MAP kinase with a possible role in cytokinesis in tobacco cells J. Cell Sci., January 10, 1998; 111(20): 3091 - 3100. [Abstract] [PDF]
|
|
|
|
|
|
K. I.-P. J. Hidari, A. S. Weyrich, G. A. Zimmerman, and R. P. McEver Engagement of P-selectin Glycoprotein Ligand-1 Enhances Tyrosine Phosphorylation and Activates Mitogen-activated Protein Kinases in Human Neutrophils J. Biol. Chem., November 7, 1997; 272(45): 28750 - 28756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Calderini, N. Glab, C. Bergounioux, E. Heberle-Bors, and C. Wilson A Novel Tobacco Mitogen-activated Protein (MAP) Kinase Kinase, NtMEK1, Activates the Cell Cycle-regulated p43Ntf6 MAP Kinase J. Biol. Chem., May 18, 2001; 276(21): 18139 - 18145. [Abstract] [Full Text] [PDF]
|
|
